R01HD105018
Project Grant
Overview
Grant Description
Immuno-isolating capsule for delivery of cell-based therapy for restoration of ovarian endocrine function in an animal model - Premature ovarian insufficiency (POI) is a common complication of anticancer treatments, such as chemotherapy and bone marrow transplantation, due to treatment toxicity.
In female cancer survivors, POI causes sterility and loss of the ovarian endocrine function, which in turn results in premature osteopenia, muscle wasting, and accelerated cardiovascular disease. These long-lasting effects are significant, particularly for young girls reaching puberty.
Our results in an ovariectomized adult mouse model have demonstrated that transplantation of an ovarian allograft encapsulated in an immunoisolating hydrogel-based capsule restores normal physiological endocrine ovarian function without eliciting immune rejection.
Yet, rodents present limitations for clinical translation to humans, such as 1) the small size of a prepubertal female limits intervention before puberty, and onset of puberty is regulated differently in primates than in rodents; 2) the small size and multiovulatory character of the mouse ovaries have limited translational potential; and 3) the differences in immune response limit the reach of our findings.
To overcome these challenges and increase the translational potential, we propose to extend preclinical testing of our therapy into non-human primates (NHPs). We will test the efficacy of encapsulated ovarian allograft to initiate physiological puberty in adolescent NHPs. We will study the longevity of graft function as well as the dynamics of the recipient's immune response to initial and repeat implantations and evaluate the quality of oocytes grown in capsules for fertility restoration.
If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian endocrine function in young women with POI.
We have demonstrated in an ovariectomized adult mouse model that implantation of an ovarian allograft encapsulated in an immunoisolating hydrogel-based capsule restores normal physiological endocrine ovarian function without eliciting immune rejection.
Yet, rodents present limitations for clinical translation to humans, such as the small size of a prepubertal female, which limits intervention before puberty, and the differences in allo-immune response between rodents and humans.
The proposed research to overcome these challenges and increase the translational potential, we propose to extend preclinical testing of our therapy into non-human primates (NHPs). We will test the efficacy of encapsulated ovarian allograft to initiate physiological puberty in adolescent NHPs. We will study the longevity of graft function as well as the dynamics of the recipient's immune response to initial and repeat implantations and evaluate the quality of oocytes grown in capsules for fertility restoration.
If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian endocrine function in young women with POI.
In female cancer survivors, POI causes sterility and loss of the ovarian endocrine function, which in turn results in premature osteopenia, muscle wasting, and accelerated cardiovascular disease. These long-lasting effects are significant, particularly for young girls reaching puberty.
Our results in an ovariectomized adult mouse model have demonstrated that transplantation of an ovarian allograft encapsulated in an immunoisolating hydrogel-based capsule restores normal physiological endocrine ovarian function without eliciting immune rejection.
Yet, rodents present limitations for clinical translation to humans, such as 1) the small size of a prepubertal female limits intervention before puberty, and onset of puberty is regulated differently in primates than in rodents; 2) the small size and multiovulatory character of the mouse ovaries have limited translational potential; and 3) the differences in immune response limit the reach of our findings.
To overcome these challenges and increase the translational potential, we propose to extend preclinical testing of our therapy into non-human primates (NHPs). We will test the efficacy of encapsulated ovarian allograft to initiate physiological puberty in adolescent NHPs. We will study the longevity of graft function as well as the dynamics of the recipient's immune response to initial and repeat implantations and evaluate the quality of oocytes grown in capsules for fertility restoration.
If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian endocrine function in young women with POI.
We have demonstrated in an ovariectomized adult mouse model that implantation of an ovarian allograft encapsulated in an immunoisolating hydrogel-based capsule restores normal physiological endocrine ovarian function without eliciting immune rejection.
Yet, rodents present limitations for clinical translation to humans, such as the small size of a prepubertal female, which limits intervention before puberty, and the differences in allo-immune response between rodents and humans.
The proposed research to overcome these challenges and increase the translational potential, we propose to extend preclinical testing of our therapy into non-human primates (NHPs). We will test the efficacy of encapsulated ovarian allograft to initiate physiological puberty in adolescent NHPs. We will study the longevity of graft function as well as the dynamics of the recipient's immune response to initial and repeat implantations and evaluate the quality of oocytes grown in capsules for fertility restoration.
If successful, this approach will offer a clinically relevant and unexplored tool to restore ovarian endocrine function in young women with POI.
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Ann Arbor,
Michigan
481082744
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 390% from $675,370 to $3,310,946.
Regents Of The University Of Michigan was awarded
Immuno-isolating Capsule for Ovarian Function Restoration in POI
Project Grant R01HD105018
worth $3,310,946
from the National Institute of Child Health and Human Development in August 2022 with work to be completed primarily in Ann Arbor Michigan United States.
The grant
has a duration of 4 years 9 months and
was awarded through assistance program 93.865 Child Health and Human Development Extramural Research.
The Project Grant was awarded through grant opportunity NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 6/22/26
Period of Performance
8/15/22
Start Date
5/31/27
End Date
Funding Split
$3.3M
Federal Obligation
$0.0
Non-Federal Obligation
$3.3M
Total Obligated
Activity Timeline
Subgrant Awards
Disclosed subgrants for R01HD105018
Transaction History
Modifications to R01HD105018
Additional Detail
Award ID FAIN
R01HD105018
SAI Number
R01HD105018-2748190385
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75NT00 NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development
Funding Office
75NT00 NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development
Awardee UEI
GNJ7BBP73WE9
Awardee CAGE
03399
Performance District
MI-06
Senators
Debbie Stabenow
Gary Peters
Gary Peters
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute of Child Health and Human Development, National Institutes of Health, Health and Human Services (075-0844) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,340,893 | 100% |
Modified: 6/22/26